Abstract: Postsynaptic differentiation of dendrites is an
essential step in synapse formation. We report here a requirement for the
transcription factor myocyte enhancer factor 2A (MEF2A) in the morphogenesis of
postsynaptic granule neuron dendritic claws in the cerebellar cortex. A
transcriptional repressor form of MEF2A that is sumoylated at lysine-403
promoted dendritic claw differentiation. Activity-dependent calcium signaling
induced a calcineurin-mediated dephosphorylation of MEF2A at serine-408 and,
thereby, promoted a switch from sumoylation to acetylation at lysine-403, which
led to inhibition of dendritic claw differentiation. Our findings define a
mechanism underlying postsynaptic differentiation that may modulate
activity-dependent synapse development and plasticity in the brain.